Albumin, in particular human serum albumin (hereinafter denoted as "HSA"), is a principal protein of blood plasma. The protein is produced in the liver and has a crucial role in maintaining normal osmotic pressure in the circulatory system. HSA also functions as a carrier for various serum molecules.
HSA is administered to patients in various clinical situations. For example, patients with shock or burn generally require repeated administration of HSA for restoring normal blood volume and thereby alleviating certain trauma-associated symptoms. Patients with hypoproteinemia or fetal erythroblastosis may require treatment with HSA. Therefore the basic therapeutic significance of HSA administration lies in treatment of fluid loss, for example in surgical operation, shock, burn or edema-inducing hypoproteinemia.
At present, HSA is produced primarily by fractionation of collected blood. The production method is disadvantageous because it is uneconomical and blood increasingly is difficult to procure. Furthermore, blood may contain unwelcome substances, for example hepatitis viruses. Accordingly, it will be helpful to develop an alternative source of HSA.
Meanwhile, the advent of recombinant DNA technology has made it possible to produce a variety of useful polypeptides in microorganisms. A number of mammalian polypeptides, for example human growth hormone and interferons have been produced in various microorganisms. The recombinant proteins have a variety of uses, such as vaccines, hormones, enzymes and antibodies.
To overcome some of the above-mentioned difficulties in the production of HSA, methods of producing HSA in large quantities using genetic engineering techniques and highly purifying the recombinant HSA have been attempted.
However, while serum-derived HSA originally has a yellow or yellowish brown color, genetically engineered HSA has a dark yellow or dark yellowish brown color. Raw materials contain certain coloring contaminants that bind to the HSA causing coloration of HSA during the production and purification thereof. The contaminants cannot be removed to a satisfactory extent by known methods of purifying serum-derived HSA.